Cytogenetics Board Review Questions

Front 1

H1. Which of the following syndromes results from a chromosome deletion in a major proportion of cases?
A. CHARGE syndrome
B. Fragile X syndrome
C. Mowat-Wilson syndrome
D. Prader-Willi syndrome
E. Charcot-Marie-Tooth syndrome

Back 1

H1. Prader-Willi is associated with deletions in 15q. The other disorders are commonly the result of other mechanisms.
The correct answer is D.

Front 2

H2. Microdeletions and duplications mediated by segmental duplications are recurrent due to their underlying mechanism. Which of the following disorders is the most common recurrent microdeletion syndrome?
A. Aniridia-Wilms tumor
B. Retinoblastoma
C. Prader-Willi syndrome
D. VCF/DiGeorge syndrome
E. Cri-du-chat syndrome

Back 2

H2. 22q11 deletion syndrome--including DiGeorge syndrome and VCF (velocardiofacial syndrome) is the most common deletion syndrome in humans, occurring in ~1/4000 births. This is a common, recurrent microdeletion mediated by NAHR of flanking low-copy repeats (LCRs). Other LCR genomic disorders (PWS, AS, Williams, Smith-Magenis, Sotos) occur at ~1/10,000- 1/20,000. Random deletion syndromes such as cri du chat, Wolf-Hirschhorn, Miller-Dieker syndrome, retinoblastoma, aniridia-Wilms tumor are less common (1/50,000-1/100,000 or less). The correct answer is D.

Front 3

H3. A 2-year-old boy presents with a history of retinoblastoma, dysmorphic features and developmental delay. Which of the following molecular abnormalities is the most likely cause of his clinical findings?
A. Nonsense mutation in the RB1 gene.
B. Missense mutation in the RB1 gene.
C. RB2 gene mutation
D. Contiguous gene deletion of 13q14
E. Contiguous gene deletion of Xq27.3.

Back 3

H3. The patient has additional clinical features (dysmorphic features and developmental delay) to retinoblastoma, suggesting a larger deletion that includes more genes than just the RB1 gene The correct answer is D.

Front 4

H4. A young woman with severe mental retardation, short stature, and other malformations has a karyotype of 45,X/46,X,r(X). Which of the following explanations is most likely to account for the constellation of clinical features noted above?
A. Both X chromosomes are likely to be active in the cells with 46 chromosomes.
B. The normal X is likely to be inactive in most or all of the cells with 46 chromosomes.
C. The ring X is likely to be acentric explaining its absence in the 45,X cell line.
D. The ring X is likely to be inactive in most or all of the cells with 46 chromosomes.
E. The XIST gene will almost certainly be present on the ring X chromosome.

Back 4

H4. The abnormal phenotypes seen in association with mosaic karyotypes of the type indicated are associated with failure of X inactivation. This is usually also associated with lack of expression of the XIST gene. This means that both the normal X and the ring X are likely to be active. The XIST gene is considerably more likely to be deleted than to be present on the ring X, although deletion of the X inactivation center may be more pertinent than deletion of the XIST gene. As mentioned above, both X chromosomes are likely to be active. The ring is not likely to be acentric.
The correct answer is A.

Front 5

H5. A middle-aged couple visits prenatal clinic for preconception counseling. Based on the wife’s age their risk of having a child with Down syndrome is increased. The genetic counselor explains that even if their pregnancy were to result from a trisomy 21 conception there is a reduced likelihood that the pregnancy would lead to a liveborn infant. Which of the following probabilities best represents the likelihood that a trisomy 21 conception will result in a liveborn infant?
A. 1% B. 20% C. 70% D. 90% E. 100%

Back 5

H5. The probability that a trisomy 21 conception will result in live birth is approximately 20%.
The correct answer is B.

Front 6

H6. Which of the following chromosome abnormalities is mostly likely constitutional?
A. t(8;21)(q22;q22)
B. t(11;22)(q23;q11.2)
C. del(5)(q22q33)
D. inv(16)(p13q22)
E. t(15;17)(q22;q21)

Back 6

H6. the 11;22 translocation is the most common non-Robertsonian translocation observed in constitutional cytogenetic studies The correct answer is B.

Front 7

H7. Triploidy is the result of three copies of each human chromosome and is one of the most common causes of spontaneous miscarriage. Which of the following occurrences is the most common mechanism by which triploidy arises?
A. chimerism
B. duplication of an entire maternal haploid chromosome set
C. one egg fertilized by two sperm
D. tetraploid conception with loss of one copy of each chromosome
E. two eggs fertilized by one sperm

Back 7

H7. Polyspermy is the most common cause of triploidy. Chimerism may caused by the fusion of two embryos and differs from mosaicism. The other options are not likely to be observed. The correct answer is C.

Front 8

H8. A newborn presents with microcephaly, hypotonia, and a high-pitched cat-like cry? Which of the following cytogenetic abnormalities is most likely to be found on chromosomal analysis?
A. 4p deletion
B. 5p deletion
C. 5q deletion
D. 8p deletion
E. 11p deletion

Back 8

H8. The features described fit Cri du Chat syndrome which typically results from terminal deletion 5p from band 5p15.2 to 5pter. 4p- syndrome results in Wolf-Hirschorn syndrome. 5q- and 8p- syndromes do not have alternative names. 11p- deletion is associated with WAGR syndrome. The correct answer is B.

Front 9

H9. A child is born with a partial deletion and partial duplication involving the same chromosome. Which of the following parental chromosomal abnormalities is most likely to lead to this occurrence?
A. balanced reciprocal translocation
B. balanced Robertsonian translocation
C. isochromosome
D. pericentric inversion
E. paracentric inversion

Back 9

H9. The occurrence of a deletion and duplication involving the terminal portions of the same chromosome is typically the result if one parent carries a pericentric inversion. This occurs if there is a cross-over within the inversion loop at meiosis. The correct answer is D.

Front 10

H10. Chorionic villus sampling is performed on a 38-year-old woman who is concerned about having a child with a chromosomal disorder. Which one of the following karyotypes carries the highest risk for this woman to deliver a chromosomally abnormal livebom?
A. 45,XX,der(13;14)(q10;q10)
B. 45,XY,der (14;21)(q10;q10)
C. 46,XY,inv(2)(p11.2q13)
D. 46,XX,inv(2)(q31q35)
E. 46,XX,t(11;22)(q23;q11.2)

Back 10

H10. Both maternal and paternal carriers of rob(13q14q) have about a 1% chance of having a child with translocation trisomy 13. Fathers who carry rob(14q21q) have less than a 1% chance of having a child with translocation Down syndrome. Both types of inversions, regardless of the parental origin, have almost no chance of abnormal offspring. The pericentric inversion (C) is a common inversion found in the population and the paracentric inversion (D) would result in nonviable dicentric and acentric products. Mothers who carry the t(11;22) are at a 6% risk for an abnormal offspring typically have 47 chromosomes with a small extra der(22) and have mental retardation and other anomalies.
The correct answer is E.

Front 11

H11. Which of the following prenatal testing methods can detect confined placental mosaicism?
A. amniocentesis
B. chorionic villus sampling C. fetal cells in maternal blood
D. maternal blood
E. percutaneous umbilical blood sampling

Back 11

H11. CVS samples chorionic villi from the placenta and can detect the mosaicism. The other tissues sampled do not include placental cells and will not allow for detection of mosaicism confined to the placenta. The correct answer is B.

Front 12

H12. A young woman is found to have a balanced translocation after a family history and pedigree analysis, during a preconception counseling visit, raised a red flag for a chromosomal abnormality. Based on this clinical finding, which of the following statements about chromosomal segregation and possible offspring is the most likely clinical outcome?
A. Offspring resulting from alternate segregation will be chromosomally normal.
B. Offspring resulting from alternate segregation are likely to be phenotypically normal.
C. Offspring resulting from adjacent-1 segregation will be chromosomally normal.
D. Offspring resulting from adjacent-1 segregation are likely to be phenotypically normal.
E. Offspring resulting from adjacent-2 segregation are likely to be phenotypically normal.

Back 12

H12. Alternate segregation results in normal gametes and in gametes with balanced chromosomal translocation. Thus the offspring are phenotypically normal but not chromosomally normal in all cases. Offspring from adjacent-1 or adjacent-2 segregation will all be unbalanced and all will be chromosomally abnormal. They would also be phenotypically abnormal, except in very unusual circumstances. Adjacent segregation-1 is when homologous centromeres segregate, in contrast to adjacent-2 where the homologous centrmorees go to the same cell. Adjacent-2 is rare compared to adjacent-1.
The correct answer is B.

Front 13

H13. During meiosis, homologs must pair in order for recombination to occur. Which of the following events allows optimal pairing and normal segregation:
A. One or more chiasma per chromosome
B. Two or more chiasma per chromosome arm
C. Distal position of chiasma on chromosome arm
D. Medial position of chiasma on chromosome arm
E. Centromere pairing of chromosomes

Back 13

H13. Optimal pairing includes one chiasma per chromosome arm, or two per chromosome.
The correct answer is A.

Front 14

H14. Which of the following microarray confirmation methods can allow the cytogeneticist to determine the mechanism of an imbalance detected on comparative genome hybridization studies?
A. Fluorescence In Situ Hybridization (FISH)
B. Junction fragment PCR
C. Multiplex ligation-dependent probe amplification (MLPA)
D. Quantitative PCR
E. Targeted microarray for the abnormal region

Back 14

H14. Only FISH can show the localization of the signal on chromosomes and allow for a determination of the mechanism for the imbalance. The correct answer is A

Front 15

H15 If you were a T-lymphocyte destined for cytogenetic analysis, some of the treatments you would experience along the way (in correct order) are:
A. B. C. D. E.
A. Hypotonic solution, acetic acid, Giemsa, trypsin
B. Hypotonic solution, lysis buffer, trypsin, Giemsa
C. Phytohemagglutinin, hypotonic solution, fixative, Colcemid, Giemsa
D. Phytohemagglutinin, Colcemid, hypotonic solution, fixative, trypsin
E. Trypsin, acetic acid, hypotonic solution, Giemsa

Back 15

H15. T-lymphocytes are stimulated to a blast phase with the red kidney bean extract phytohemagglutinin (PHA). After 48-72 hours, a mitotic poison such as Colcemid or colchicine is used to block spindle formation and attachment to “arrest” cells in mitosis, a hypotonic treatment is used to swell the cells, they are fixed in 3:1 methanol:acetic acid, put onto slides, and then most often treated with trypsin prior to Giemsa staining to produce G-banding patterns. The correct answer is D.

Front 16

H16. The historical milestones in cytogenetics mark exciting intervals in the development of the field of clinical genetics. Which of the following series of events follows the chronological order in which these milestones were attained?
A. Hypotonic treatment of cells > Correct chromosome number is 46 > Y chromosome identified in humans > Chromosome banding techniques>Fragile sites and fragile X syndrome
B. Correct chromosome number is 46 >Hypotonic treatment of cells > Y chromosome identified in humans > Chromosome banding techniques> Fragile sites and fragile X syndrome
C. Y chromosome identified in humans >Hypotonic treatment of cells > Correct chromosome number is 46 > Chromosome banding techniques> Fragile sites and fragile X syndrome D. Hypotonic treatment of cells > Y chromosome identified in humans> Correct chromosome number is 46 > Chromosome banding techniques> Fragile sites and fragile X syndrome
E. Y chromosome identified in humans> Hypotonic treatment of cells > Correct chromosome number is 46 > Fragile sites and fragile X syndrome >Chromosome banding techniques>

Back 16

H16. The discovery of the Y Chromosome and the XX/XY mechanism of sex determination in humans was by T. S. Painter in 1923, hypotonic treatment of cells by T. C. Hsu in 1953, the correct chromosome number by Tjio and Levan in 1956, chromosome banding techniques in 1969/70, and fragile sites and fragile X in the late 70s.
The correct answer is C.

Front 17

H17. A newborn presents with a cardiac defect, cleft palate and a hypoplastic thymus. Which of the following chromosome abnormalities is the most likely cytogenetic imbalance in this patient?
A. A deletion of 1q.21.1
B. A deletion of 2q11.1
C. A deletion of 16p11.2
D. A deletion of 22q11.2
E. A deletion of 22q13.3

Back 17

H17. Deletion 22q11.2 causes VCF/DiGeorge syndrome. The three phenotypic characteristics listed are most consistent with a clinical diagnosis of 22q11.2 deletion. The correct answer is D.

Front 18

H18. The mammalian somatic cell cycle is approximately 24 hours in length. Which of the following phases of the cell cycle requires the most time?
A. G1 B. S C. G2 D. Interphase E. Mitosis

Back 18

H18. The correct answer is D. All of the phases of mitosis take approximately one hour.

Front 19

H19. Meiotic recombination is necessary for genetic diversity and rates of genetic recombination are different in males than females and for different chromosomal regions. The highest rate of recombination is observed in which of the following situations?
A. in females compared to males near centromeres
B. in males compared to females near centromeres
C. in males compared to females in the middle of each chromosome arm
D. near centromeres compared to near telomeres
E. near telomeres compared to near centromeres

Back 19

H19. Overall, recombination rates in human females are significantly higher (~50%) than males, except near telomeres, where male recombination rates are higher than female. Human recombination is about twice as high as that in mouse, perhaps due to our biarmed chromosomes compared to all telocentric chromosomes in mice (remember the obligatory 1 crossover per chromosome arm for stable pairing and segregation). Recombination is suppressed near centromeres, and increases greatly near telomeres in both males and females (but more so in males).
The correct answer is E..

Front 20

H20. An MRI shows lissencephaly in your patient, however the patient does not have any dysmorphic facial features. Which of the following is the most likely mutation?
A. Point mutation within the LIS1 gene coding region.
B. Terminal deletion of 17p which includes the LIS1 gene
C. Terminal deletion of 17q which includes the LIS1 gene
D. Terminal duplication of 17p which includes the LIS1 gene E. Triplet repeat expansion involving the LIS1 gene

Back 20

H20. Point mutations within the LIS1 gene cause Isolated Lissencephaly syndrome. These individuals can only exhibit lissencephaly without the more dysmorphic features that are associated with Miller-Dieker syndrome, which is caused by larger deletions of 17p. The correct answer is A

Front 21

H21. G-banding has been the preferred method for cytogenetic analysis since the late 1960s. The underlying DNA content corresponds to the staining pattern observed by G-banding. Which of the following descriptions details the difference(s) between G-negative bands and G-positive bands?
A. G-negative bands are more gene rich than G-positive bands
B. G-positive bands are GC rich regions and are early replicating C.
G-negative bands are AT rich and are late replicating
D. G-negative bands are GC rich and are late replicating
E. G-positive bands are more gene rich than G-negative bands

Back 21

H21. R-bands are the reverse of G-bands, so there are the same number of each. G-positive bands are AT-rich and relatively later replicating. The correct answer is A

Front 22

H22. Structural chromosome abnormalities result from an assortment of molecular mechanisms. Our knowledge is most complete for which of the following specific molecular mechanisms?
A. terminal deletion
B. interstitial deletion
C. isochromosome
D. reciprocal translocation
E. ring chromosome

Back 22

H22. B is correct. Common, recurrent micodeletions (22q11, 17p11, 15q11-q13, etc.) are interstitial deletions with flanking low-copy repeats (LCRs) with very high sequence homology. In meiosis, mispairing of proximal and distal copies (non-allelic homologous recombination, NAHR), leads to unequal cross-over producing deletion or duplication. Specific mechanisms at a sequence level are not known for other classes of structural chromosome rearrangements.
The correct answer is B

Front 23

H23. Comparative genomic hybridization (CGH) is one method that can be used for copy number variation (CNV) detection. Which of the following issues is a limitation of this methodology compared to a G-banded karyotype?
A. Cannot detect polyploidies
B. Cannot detect single copy differences
C. Cannot detect unbalanced translocations
D. Lower resolution than G-banded karyotype
E. Requires cells to be cultured

Back 23

A